Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Nancy M. Albert, PhD, RN, FAHA

Biykem Bozkurt, MD, PhD, FACC, FAHA

Ralph G. Brindis, MD, MPH, MACC

Mark A. Creager, MD, FACC, FAHA[#][1]

Lesley H. Curtis, PhD, FAHA

David DeMets, PhD[#][1]

Robert A

/pdf/2014-aha-acc-hrs-guideline-for-the-management-of-patients-1v8ficsqox.pdf

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

Oral bioavailability measurements in rats for over 1100 drug candidates studied at SmithKline Beecham Pharmaceuticals (now GlaxoSmithKline) have allowed us to analyze the relative importance of molecular properties considered to influence that drug property. Reduced molecular flexibility, as measured by the number of rotatable bonds, and low polar surface area or total hydrogen bond count (sum of donors and acceptors) are found to be important predictors of good oral bioavailability, independent of molecular weight. That on average both the number of rotatable bonds and polar surface area or hydrogen bond count tend to increase with molecular weight may in part explain the success of the molecular weight parameter in predicting oral bioavailability. The commonly applied molecular weight cutoff at 500 does not itself significantly separate compounds with poor oral bioavailability from those with acceptable values in this extensive data set. Our observations suggest that compounds which meet only the two cr...

Molecular properties that influence the oral bioavailability of drug candidates.

https://www.cell.com/cell/pdf/S0092-8674(00)80949-6.pdf

Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior

/pdf/cdc-guideline-for-prescribing-opioids-for-chronic-pain-48d7kdjqlr.pdf

CDC guideline for prescribing opioids for chronic pain

A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment

The Pharmacological Basis of Therapeutics

The Pharmacological Basis of Therapeutics.

The pharmacological basis of therapeutics

Eight clinically employed antiepileptic drugs have been tested for anticonvulsant potency at their time of peak effect in mice and rats by a battery of four assay procedures, as follows : maximal electroshock seizure pattern, minimal electroshock seizure threshold, hyponatremic electroshock seizure threshold and Metrazol seizure threshold. In addition, minimal neurological toxicity was determined. On the basis of the results obtained, the following conclusions have been reached: 1) The apparent discrepancies in drug potencies reported for mice and rats can be explained in a large measure on the basis of assay technic, especially by failure to test the drugs at the time of peak effect in the two species. 2) When proper precautions in technics are observed, the profiles of anticonvulsant activity of the various clinically employed antiepileptics are reasonably similar in the two species. 3) Most of the drugs tested were more potent in rats by the maximal electroshock seizure pattern test, and more potent in mice by the remaining three assay tests. 4) In general, phenobarbital was most potent and most toxic and Tridione, Paradione and Phenurone were least potent and least toxic by all tests in both species. 5) The mouse is as suitable as the rat for anticonvulsant screening purposes and in some respects this species is to be preferred. However, because of reasons presented in the discussion, it would seem prudent to use more than one species for the definitive comparison of antiepileptic agents. Attention has been called to the details of anticonvulsant assay procedures in mice and rats and the important differences in assay technic in the two species. In addition, a number of special precautions have been described, the observance of which contributes to the ease and precision of assay. Caution in the interpretation of anticonvulsant assay data is urged. Unless the candidate antiepileptic agents under investigation are chemically related to compounds known to possess clinical anticonvulsant usefulness, the assay results obtained by currently available methods may have only limited value for predicting clinical efficacy or specificity for various seizure types.

Louis S. Goodman

Papers

The Pharmacological Basis of Therapeutics

The Pharmacological Basis of Therapeutics

The Pharmacological Basis of Therapeutics.

The pharmacological basis of therapeutics

Comparative assays of antiepileptic drugs in mice and rats